Photodynamic therapy, hereinafter also referred to as “PDT”, is a process for treating cancer wherein visible light is used to activate a substance, such as a dye or drug, which then attacks the tumor tissue through one or more photochemical reactions, thereby producing a cell-killing, or cytotoxic, effect. It has been discovered that when certain photosensitizer compounds are applied to the human or animal body, they are selectively retained by cancerous tissue while being eliminated by healthy tissue. The tumor or cancerous tissue containing the photosensitizer can then be exposed to therapeutic light of an appropriate wavelength and at a specific intensity for activation. The light energy and the photosensitizer cause a photochemical reaction which kills the cells in which the photosensitizer resides.
Phthalocyanines, hereinafter also abbreviated as “Pcs”, are a group of photosensitizer compounds having the phthalocyanine ring system. Phthalocyanines are azaporphyrins consisting of four benzoindole groups connected by nitrogen bridges in a 16-membered ring of alternating carbon and nitrogen atoms (i.e., C32H16N8) which form stable chelates with metal and metalloid cations. In these compounds, the ring center is occupied by a metal ion (either a diamagnetic or a paramagnetic ion) that may, depending on the ion, carry one or two ligands. In addition, the ring periphery may be either unsubstituted or substituted. The synthesis and use of a wide variety of phthalocyanines in photodynamic therapy is described in International Publication WO 2005/099689. Phthalocyanines strongly absorb clinically useful red or near IR radiation with absorption peaks falling between about 600 and 810 nm, which potentially allows deep tissue penetration by the light.
Phthalocyanines are generally very stable to photofading caused by 1O2. This is advantageous in many circumstances because, for example, special storage and handling techniques are not required. However, for PDT the photostability of a photosensitizer such as Pc 4 can also be disadvantageous. For example, the outer shell of a treated tumor could shield the inner core of the tumor from light and thus prevent the light necessary for the photodynamic therapy from reaching the inner core. It would therefore be advantageous in some situations to be able to formulate phthalocyanines in such a way as to decrease their stability without rendering them so unstable that they cannot function.
Phthalocyanines should be formulated to allow delivery in sufficient amounts to be therapeutically effective. Phthalocyanines such as Pc 4 have typically been formulated for systemic delivery in a solution of povidone, which is subsequently dissolved in a solution of Cremophor EL, ethanol, and saline (5:5:90 by volume), to provide phthalocyanine at a concentration of about 0.1 mg/mL for clinical use. For topical delivery, phthalocyanines have been formulated in a solution of povidone which is subsequently dissolved in a solution of Cremophor EL, ethanol, and propylene glycol (5:68:27 by volume), to again provide a concentration for clinical use of about 0.1 mg/mL. However, while these formulations are useable, they can be slow to provide effective concentrations of the phthalocyanine at the tumor site. In addition, the relative performance of various phthalocyanine salts in phthalocyanine formulations remains unknown.
Accordingly, there remains a need for the characterization of additional phthalocyanine salts and the development of additional formulations for their administration.